Scrub typhus presenting as acute abdomen

Scrub typhus, a zoonosis, is a systemic febrile illness with diverse clinical manifestations. It may also present with signs and symptoms of acute abdomen. We present two serologically confirmed cases of scrub typhus presenting with acute abdomen that were managed conservatively with antibiotics.     

Rapid Increase in Scrub Typhus Incidence in Mainland China, 2006–2014

Scrub typhus is a vector-borne disease, which has recently reemerged in China. In this study, we describe the distribution and incidence of scrub typhus cases in China from 2006 to 2014 and quantify differences in scrub typhus cases with respect to sex, age, and occupation. The results of our study indicate that the annual incidence of scrub typhus has increased during the study period. The number of cases peaked in 2014, which was 12.8 times greater than the number of cases reported in 2006. Most (77.97%) of the cases were reported in five provinces (Guangdong, Yunnan, Anhui, Fujian, and Shandong). Our study also demonstrates that the incidence rate of scrub typhus was significantly higher in females compared to males (P < 0.001) and was highest in the 60–69 year age group, and that farmers had a higher incidence rate than nonfarmers (P < 0.001). Different seasonal trends were identified in the number of reported cases between the northern and southern provinces of China. These findings not only demonstrate that China has experienced a large increase in scrub typhus incidence, but also document an expansion in the geographic distribution throughout the country.     

Gastrointestinal manifestations of septic patients with scrub typhus in Maharat Nakhon Ratchasima Hospital

Scrub typhus is an acute febrile illness caused by Orientia induced vasculitis, which is common in Asia and the Pacific Islands and is sometimes also encountered in Western countries. Even though it can cause multi-organ dysfunctions, there is limited information regarding the relationship between scrub typhus infection and gastrointestinal dysfunction. Therefore, a cross-sectional study was conducted to discover the gastrointestinal manifestations of septic patients with scrub typhus infection. During the study period, 80 septic cases were recruited, and according to the results of immunofluorescent antibody testing (IFA), 20 (25%) were found to have scrub typhus infection. The most common gastrointestinal symptoms of scrub typhus patients were vomiting 13 (65%), nausea 12 (60%), diarrhea 9 (45%), and hametamesis or melena 5 (25%). Gastrointestinal signs included hepatomegaly 8 (40%), jaundice 7 (35%), and abdominal pain 4 (20%). Elevation of SGOT, SGPT, and alkaline phosphatase were 16 (80%), 14 (70%), and 16 (80%), respectively. Direct bilirubin was elevated in 19 (95%) of the cases and half of the cases had a low serum protein level. Of scrub typhus cases, 8 (40%) had eschars. The sites of eschars were mostly in hidden areas, such as on the back, genitalia and abdomen. Three of the five patients with eschar had hepatomegaly on ultrasound examination. The significant findings of the scrub typhus septic patients with eschar on endoscopic examination were gastritis in two cases, gastritis with gastric erosion in two cases, and one case showed a duodenal ulcer and erosion. The differentiating point for endoscopic findings in scrub typhus compared to the other causes was that the stomach lesions were more frequent and severe than the duodenal lesions. According to our endoscopic findings, physicians should be aware of gastric and duodenal lesions in febrile patients with gastrointestinal symptoms, such as abdominal pain or discomfort and indigestion. Scrub typhus can cause gastrointestinal and liver dysfunction.     

Scrub Typhus: Surveillance,Clinical Profile and Diagnostic Issues in Shandong,China

To elucidate the epidemic status, clinical profile, and current diagnostic issues of scrub typhus in Shandong Province, we analyzed the surveillance data of scrub typhus from 2006 to 2011 and conducted a hospital-based disease survey in 2010. Scrub typhus was clustered in mountainous and coastal areas in Shandong Province, with an epidemic period from September to November. The most common manifestations were fever (100%), eschar or skin ulcer (86.3%), fatigue (71.6%), anorexia (71.6%), and rash (68.6%). Predominant complications included bronchopneumonia, toxic hepatitis, and acute cholecystitis in 21.6%, 3.9%, and 2.9% of the cases, respectively. Severe complications including toxic myocarditis, heart failure, pneumonedema, pleural effusion, and emphysema were first reported in Shandong. Missed and delayed diagnosis of scrub typhus was common in local medical institutions. Alarm should be raised for changes of clinical features and current diagnostic issues of scrub typhus in newly developed endemic areas.     

Scrub typhus during pregnancy: a case report and review of the literature

Scrub typhus is a rickettsial disease that is uncommon during pregnancy. We report a case of a 33-year-old woman, G1P0, 29 weeks pregnancy who presented to hospital with high fever, chill and headache for two weeks. Her diagnosis of scrub typhus was confirmed by serum immunofluorescent assay. She was successfully treated with chloramphenicol, but preterm delivery occurred. Her infant died from respiratory distress syndrome. No vertical transmission was demonstrated in this case. Scrub typhus should be listed in the differential diagnosis of acute febrile illness in pregnant women, who either live in, or return from, endemic areas. Chloramphenicol can be used safely during pregnancy if it is not circulating at the time of delivery.     

Murine typhus identified as a major cause of febrile illness in a camp for displaced Khmers in Thailand

Scrub and murine typhus have been identified as causes of illness among the 238,000 displaced Khmer people residing in temporary settlements on the Thai side of the Thai-Cambodian border. Still, the true extent of the problem and the relative frequency of infection with scrub typhus as compared to murine typhus are unknown. We evaluated consecutive patients with unexplained pyrexia (documented fever, no exclusionary diagnosis, and constitutional symptoms) in 1 temporary settlement over 1 month. Laboratory studies included culture of blood and assay of paired sera for rickettsial IgM and IgG antibody, for dengue IgM and IgG antibody, and for leptospiral IgM and IgG antibody. Among 37 patients (27 adults and 10 children), 28 (75%) had a rickettsiosis (26 cases of murine typhus and 2 cases of scrub typhus). No case of enteric fever, dengue, or leptospirosis was diagnosed. The illnesses of 9 patients were not identified. Signs and symptoms did not distinguish confirmed rickettsial infections from undiagnosed illnesses. The 1 month attack rate of rickettsial infection was 29/100,000 for children and 185/100,000 for adults. Murine typhus was a major cause of febrile illness in this settlement.     

Molecular Confirmation of Co-Infection by Pathogenic Leptospira spp. and Orientia tsutsugamushi in Patients with Acute Febrile Illness in Thailand

Leptospirosis and scrub typhus are major causes of acute febrile illness in rural Asia, where co-infection is reported to occur based on serologic evidence. We re-examined whether co-infection occurs by using a molecular approach. A duplex real-time polymerase chain reaction was developed that targeted a specific 16S ribosomal RNA gene of pathogenic Leptospira spp. and Orientia tsutsugamushi. Of 82 patients with an acute febrile illness who had dual infection on the basis of serologic tests, 5 (6%) had polymerase chain reaction results positive for both pathogens. We conclude that dual infection occurs, but that serologic tests may overestimate the frequency of co-infections.Leptospirosis and scrub typhus are major causes of acute febrile illness in the Asia-Pacific region.^1,2 Leptospirosis is caused by pathogenic Leptospira spp., and scrub typhus is caused by the gram-negative obligate intracellular bacterium Orientia tsutsugamushi. Because both infections affect agricultural workers and have similar clinical features, including fever, myalgia, headache, and lymphadenopathy, they are difficult to distinguish on clinical grounds alone. Co-infection with leptospirosis and scrub typhus was first reported in rice farmers who were hospitalized with leptospirosis in northeastern Thailand; with 9 (40%) of 22 patients were also seropositive for scrub typhus.³ Dual infection has also been reported in Taiwan and India.^4–6 A study from Thailand reported that 103 (12.2%) of 845 patients with an acute febrile illness had dual infection, of which 33 were attributed to leptospirosis and scrub typhus.² All previous studies have relied on serologic tests, and the possibility remains that co-infection represents cross-reactivity between serologic assays, or an acute infection by one pathogen after a recent infection by another pathogen. The aim of this study was to determine if dual infection in Thai patients on the basis of serologic testing could be confirmed by a molecular method.The study protocol was approved by the Ethics Committee of the Faculty of Tropical Medicine, Mahidol University, Thailand (MUTM 2010-033-01). A duplex real-time polymerase chain reaction (PCR) was developed for the 16S ribosomal RNA (rRNA) gene. Primers and hydrolysis probe targeting the 16S rRNA gene of pathogenic Leptospira spp. were based on a reported TaqMan assay.⁷ These primers generated an 88-basepair product (positions 205–220 and 240–263 of L. interrogans 16S rRNA gene sequence; GenBank accession no. {"type":"entrez-nucleotide","attrs":{"text":"AY631894","term_id":"54112255","term_text":"AY631894"}}AY631894). Primers and hydrolysis probe targeting the 16S rRNA gene of O. tsutsugamushi were modified from those of a previous study⁸ and were as follows: forward 5′-GGCATACGGTATTAGCACTTA-3′, reverse 5′-GCATTAATTAGTGGCAAACG-3′, and probe ROX-5′-TAAA TGTTATTCCGTACTGATGGGCAG-3′-BHQ2. The hydrolysis probe for O. tstsugamushi was labeled with ROX so that this probe could be used in a single reaction with the hydrolysis probe for Leptospira spp. (6-FAM). The modified primers amplified a 92-basepair product (positions 53–72 and 125–145 of the 16S rRNA gene of O. tsutsugamushi strain Boryong; GenBank sequence accession no. {"type":"entrez-nucleotide","attrs":{"text":"NC_009488","term_id":"148283997","term_text":"NC_009488"}}NC_009488). The assay was optimized and performed in a 20-μL single reaction containing 5 μL DNA, 1× QUANTIPROBES (QuantiMix Easy Probes Kit; Biotools, Madrid, Spain), 8 mM MgCl₂, 0.15 μM of each primer, and 0.1 μM of each probe. Cycling conditions were at 95°C for 8 minutes (1 cycle), followed by 50 cycles at 95°C for 10 sec and 60°C for 1 minute.The PCR amplification efficiencies and detection limits of the assay were determined by using a linearized plasmid pG16S described for scrub typhus⁸ and genomic DNA of L. interrogans serovar Lai for leptospirosis. DNA concentration was determined by using the Quanti-it™ High-Sensitivity DNA Assay Kit (Invitrogen, Carlsbad, CA) and the Rotor-Gene 3000 by using the DNA concentration measurement mode. Serially diluted DNA for each pathogen was used as a template in four triplicate calibration curves.The mean PCR efficiency was 0.88 (95% confidence interval [CI] = 0.81–0.93) for L. interrogans and 0.97 (95% CI = 0.96–0.99) for O. tsutsugamushi. The calibration curve for Leptospira spp. had a mean slope of −3.7 (95% CI = −3.8 to −3.48) and a y intercept of 38.2 (95% CI = 36.1–40.2), and that for O. tsutsugamushi had a mean slope of −3.3 (95% CI = −3.5 to −3.2) and a y intercept of 37.5 (95% CI = 36.4–38.8). Cycle quantification ranged from 19.9 to 36 (interquartile range = 22.7–34.5) for O. tsutsugamushi, and from 14.5 to 32.2 (interquartile range = 18.7–35.9) for Leptospira spp. The calibration curve showed a linear dynamic range over five orders of magnitude (5×10⁵ to 5 copies/μL) for both pathogens. The limit of detection of a duplex quantitative PCR was five genome equivalents for Leptospira genomic DNA and five copies for the O. tsutsugamushi plasmid. The mean coefficient of variation for the quantification calibrator for leptospirosis and scrub typhus was 0.1%.The analytical specificity of the duplex PCR was evaluated by using genomic DNA isolated from one clinical isolate of each of the following species: Rickettsia typhi, Staphylococcus aureus, Enterococcus sp., Escherichia coli, Salmonella enterica serovar Typhi, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Burkholderia pseudomallei. These species were selected because they represent common causes of serious infection in Southeast Asia. Genomic DNA of O. tsutsugamushi and R. typhi was extracted from infected laboratory tissue cultures by using the Wizard^® SV Genomic DNA Purification Kit (Promega, Madison, WI). Genomic DNA was extracted from the remaining species from laboratory cultures by using the Wizard^® Genomic DNA Extraction Kit (Promega) with the addition of 5 μL (10 mg/mL) of lysostaphin during the extraction of S. aureus DNA. None of the isolate tests showed a false-positive result.Diagnostic sensitivities and specificities of the assay were determined by using patients selected from a cohort study of acute febrile illness conducted at a hospital in northeastern Thailand during October 2000–December 2001, which has been described.⁹ Blood samples were obtained at admission for Leptospira spp. culture, serologic testing, and molecular diagnostic tests, and a second (convalescent) sample was obtained for serologic testing approximately two weeks later.Diagnosis of leptospirosis was based on a positive Leptospira culture and/or positive microscopic agglutination test (MAT) result (defined as a four-fold increase in MAT titer between acute-phase and convalescence-phase samples or a single titer ≥ 1:400). Diagnosis of scrub typhus was based on a positive fluorescent antibody assay (IFA) result (defined as a four-fold increase in IgM and IgG titer in a scrub typhus IFA between acute-phase and convalescence-phase samples or an IgM titer ≥ 1:400 and an IgG titer ≥ 1:800).A case–control study was conducted from the original cohort and consisted of 100 patients with laboratory confirmed leptospirosis alone (24 of whom were culture positive for Leptospira spp.), 100 patients with scrub typhus alone, and 150 controls. The controls were randomly selected from patients with negative laboratory test results for both infections, and had the following diagnoses: dengue fever (n = 16); murine typhus (n = 7); bacterial septicemia caused by Escherichia coli (n = 5), Klebsiella pneumoniae (n = 2), Klebsiella oxytoca (n = 1), Corynebacterium jeikeium (n = 1), Enterococcus sp. (n = 1), or Pseudomonas aeruginosa (n = 1); melioidosis (n = 1); human immunodeficiency virus–related infection (n = 1); Japanese encephalitis (n = 1); Q fever (n = 1); other diagnoses (n = 19); or an unknown diagnosis (n = 93).DNA was extracted from 5 mL of admission blood samples (containing EDTA) obtained during the clinical fever study as described.⁹ Each sample was assayed in duplicate in the duplex PCR. A positive result for one or both duplicate samples for a given species was interpreted as positive. The PCR result was positive for 59 of 100 leptospirosis monoinfection cases (diagnostic sensitivity = 59.0, 95% CI = 48.7–68.7) and for 62 of 100 scrub typhus monoinfection cases (diagnostic sensitivity = 62.0, 95% CI = 51.7–71.5). The PCR result was negative for leptospirosis for 138 of 150 controls (diagnostic specificity = 92.0, 95% CI = 86.4–95.8) and negative for scrub typhus for 139 of 150 controls (diagnostic specificity = 92.7, 95% CI = 87.3–96.3).The assay was then applied to all patients in the acute febrile illness cohort study who had been defined as having dual infections and had samples available for testing (n = 82). A four-fold increase in scrub typhus IFA titer was observed for 64 patients (78%), and a high single titer was observed for 18 patients (22%). Leptospirosis was diagnosed on the basis of positive results for culture and MAT for five patients (6%), positive results for culture and negative results for MAT for three patients (4%), and negative culture results and positive results for MAT for 74 patients (90%). The duplex PCR results for these 82 patients were as follows: 43 (52%) were positive for leptospirosis, 9 (11%) were positive for scrub typhus, 5 (6%) were positive for leptospirosis and scrub typhus, and 25 (30%) were negative for leptospirosis and scrub typhus.Our findings confirm that co-infection occurs, albeit at a low frequency (6%). Possible explanations for the difference observed between serologic and molecular results include low sensitivity of the molecular assay, failure to test a sample obtained during the window of bacteremia in leptospirosis, serologic cross-reactivity, and acute infection caused by one pathogen in the background of a recent but not active infection caused by the second pathogen. The assay described could represent a useful diagnostic assay to detect both pathogens in a single test.     

Causes of acute, undifferentiated, febrile illness in rural Thailand: results of a prospective observational study

The adult patients who, between July 2001 and June 2002, presented at any of five hospitals in Thailand with acute febrile illness in the absence of an obvious focus of infection were prospectively investigated. Blood samples were taken from all of the patients and checked for aerobic bacteria and leptospires by culture. In addition, at least two samples of serum were collected at different times (on admission and 2-4 weeks post-discharge) from each patient and tested, in serological tests, for evidence of leptospirosis, rickettsioses, dengue and influenza. The 845 patients investigated, of whom 661 were male, had a median age of 38 years and a median duration of fever, on presentation, of 3.5 days. Most (76.5%) were agricultural workers and most (68.3%) had the cause of their fever identified, as leptospirosis (36.9%), scrub typhus (19.9%), dengue infection or influenza (10.7%), murine typhus (2.8%), Rickettsia helvetica infection (1.3%), Q fever (1%), or other bacterial infection (1.2%). The serological results indicated that 103 (12.2%) and nine (1%) of the patients may have had double and triple infections, respectively. Leptospirosis and rickettsioses, especially scrub typhus, were thus found to be major causes of acute, undifferentiated fever in Thai agricultural workers.     

Short report: prospective evaluation of a multi-test strip for the diagnoses of scrub and murine typhus, leptospirosis, dengue Fever, and Salmonella typhi infection

A multi-test strip dotblot immunoassay for the diagnosis of typhoid fever, scrub typhus, murine typhus, dengue virus infection and leptospirosis was evaluated in Thai adults presenting to hospital with acute, undifferentiated fever. The kit gave multiple positive test results in 33 of 36 patients with defined infections and was therefore not a useful admission diagnostic tool.     

Historical epidemics of scrub typhus in Queensland and Papua New Guinea

Undifferentiated febrile diseases (e.g., Mossman fever) from northern Queensland were eventually partially attributed to mite-transmitted rickettsial infections known as scrub typhus or tsutsugamushi fever. Scrub typhus became a major medical threat to military operations in Papua New Guinea during the Second World War and killed more Australian soldiers than malaria in the pre-antibiotic era. Further investigations showed scrub typhus to be an occupational disease of rural workers in north Queensland especially around Cairns and Innisfail. Occasional small epidemics of scrub typhus still occur during military exercises in Queensland, but as scrub typhus is not a reportable disease, its presence in the civilian community is largely unknown. Increased use of serological testing in patients with fever and rash illnesses after exposure in northern Queensland is likely to show that scrub typhus is a modern infection that remains treatable with antibiotics once it is identified.     

Orientia tsutsugamushi in peripheral white blood cells of patients with acute scrub typhus.

Scrub typhus, caused by Orientia tsutsugamushi, is an acute illness that occurs in many parts of Asia. Clinical manifestations range from inapparent to organ failure. Organisms disseminate from the skin to target organs, suggesting that they may enter the peripheral circulation. Here, peripheral blood cell smears from patients with acute scrub typhus were obtained before treatment and for 2 days after treatment and reacted with antibodies specific for O. tsutsugamushi. White blood cells from 3 of 7 patients with acute scrub typhus stained positively for O. tsutsugamushi. Cells containing O. tsutsugamushi were mononuclear and were detected on each day of sampling. The presence of O. tsutsugamushi in peripheral white blood cells of patients with acute scrub typhus is a new finding with clinical and pathogenic implications.     

Septic shock secondary to scrub typhus: characteristics and complications

Scrub typhus is an acute febrile illness caused by infection with Orientia tsutsugamushi transmitted by the bite of larval trombiculid mites (chiggers). A prospective study was conducted in septic shock patients in Maharat Hospital, Nakhon Ratchasima Province, Thailand, from 12 November 2001 to 5 January 2002. Of the 51 septic shock patients studied during the 7 week period, 18 (35.3%) were found to have evidence of scrub typhus infection; 3 patients (16.7%) died. In this study, septic shock caused by Orientia tsutsugamushi is the most prominent (35.3%) in endemic area of scrub typhus. Scrub typhus with septic shock patients results in organ failure: respiratory failure, DIC were predominant, followed by renal and hepatic involvement. Two deaths were due to respiratory failure and one death was as a result of combined respiratory and renal failure. Fever was the most common symptom, followed by headache, myalgia and dyspnea; lymphadenophathy and eschar are common signs. Laboratory findings revealed that almost all of the patients had a mild leukocytosis, reduced hematocrit and thrombocytopenia; SGOT, ALP, direct bilirubin (DB), total billirubin (TB), BUN, Cr were elevated; hypoalbuminemia was noted. Urinalysis showed that 88.9% of the patients had albuminuria. 77.8% of patients had abnormal chest X-rays.     

Rickettsial infections and their clinical presentations in the Western Province of Sri Lanka: a hospital-based study.

BACKGROUND: Rickettsial infections are re-emerging. A study of the geographical distribution of rickettsial infections, their clinical manifestations, and their complications would facilitate early diagnosis. METHODS: Thirty-one selected patients from the Western Province of Sri Lanka were studied for rickettsial species, clinical manifestations, and complications. RESULTS: Of 31 patients with possible rickettsioses, 29 (94%) fell into the categories of confirmed, presumptive, or exposed cases of acute rickettsial infections (scrub typhus was diagnosed in 19 (66%), spotted fever group in eight (28%)). Early acute infection or past exposure was suggested in two (7%) cases; cross-reactivity of antigens or past exposure to one or more species was suggested in nine (31%). Seventeen out of 19 (89%) patients with scrub typhus had eschars. Nine out of 29 (32%) patients had a discrete erythematous papular rash: seven caused by spotted fever group, two by scrub typhus. Severe complications were pneumonitis in eight (28%), myocarditis in five (17%), deafness in four (14%), and tinnitus in two (7%). The mean duration of illness before onset of complications was 12.0 (SD 1.4) days. All patients except one made a good clinical recovery with doxycycline or a combination of doxycycline and chloramphenicol. CONCLUSIONS: In a region representing the low country wet zone of Sri Lanka, the main rickettsial agent seems to be Orientia tsutsugamushi. Delay in diagnosis may result in complications. All species responded well to current treatment.     

Evaluation of a newly developed dipstick test for the rapid diagnosis of scrub typhus in febrile patients

Scrub typhus is a potentially fatal, febrile disease prevalent in rural Asia. The etiological agent, Orientia tsutsugamushi, is transmitted to humans by the bite of a larval trombiculid mite. No current diagnostic test is sufficiently practical for use by physicians working in rural areas. A new dipstick test using a dot blot immunoassay format has been developed for the serodiagnosis of scrub typhus. We evaluated this test on 83 patients presenting with acute fever of unknown origin at Maharaj Hospital, a tertiary care medical center in Nakhon Ratchasima, Northeast Thailand. The diagnosis of scrub typhus was confirmed in 30 of these patients (36%) by the indirect immunoperoxidase test. The sensitivity of the test was 87% and its specificity was 94%. The dot blot immunoassay dipstick is accurate, rapid, easy to use, and relatively inexpensive. It appears to be the best currently available test for diagnosing scrub typhus in rural areas where this disease predominates.     

Bilateral simultaneous facial palsy following scrub typhus meningitis: a case report and literature review

Scrub typhus is widely distributed across the Asia-Pacific region, Taiwan included. The clinical manifestations and complications of scrub typhus vary and the illness ranges in severity from mild to fatal. The etiology of facial nerve palsy varies and infectious agents have been associated with this condition. Rickettsiae species have, however, rarely been reported as the causative agents. We report the case of a 49-year-old man who had fever, malaise, headache, oligouria and tea-colored urine. Bilateral pneumonitis, acute renal failure, acalculous cholecystitis and aseptic meningitis were diagnosed after a series of examinations. The patient recovered after doxycycline treatment but he developed bilateral facial palsy during the convalescent phase, which improved after the administration of a steroid. The diagnosis of infection with Orientia tsutsugamushi was confirmed by the Taiwan Center of Disease Control and the tests for Leptospira, Rickettsia typhi and Coxiella burnetii were all negative. This case indicates that scrub typhus needs to be included in the differential diagnoses of cases of bilateral and simultaneous facial nerve palsy, particularly in areas where the disease is endemic.     

Scrub typhus hepatitis confirmed by immunohistochemical staining

Scrub typhus is an acute febrile disease caused by Orientia tsutsugamushi (O. tsutsugamushi). We report herein the case of a woman who presented with fever and elevated serum levels of liver enzymes and who was definitively diagnosed with scrub typhus by histopathological examination of liver biopsy specimens, serological tests and nested polymerase chain reaction. Immunohistochemical staining using a monoclonal anti-O. tsutsugamushi antibody showed focally scattered positive immunoreactions in the cytoplasm of some hepatocytes. This case suggests that scrub typhus hepatitis causes mild focal inflammation due to direct liver damage without causing piecemeal necrosis or interface hepatitis. Thus, scrub typhus hepatitis differs from acute viral hepatitis secondary to liver damage due to host immune responses, which causes severe lobular disarray with diffuse hepatocytic degeneration, necrosis and apoptosis as well as findings indicative of hepatic cholestasis, such as hepatic bile plugs or brown pigmentation of hepatocytes.     

Short report: Abnormal liver function in scrub typhus

Scrub typhus is one kind of rickettsial disease and may cause fever, cough, and skin rashes in infected humans. Regarding liver involvement, it was uncommon to be reported in previous medical literature from Western countries. This study observes the relationship between scrub typhus and liver function. From January 1998 to August 2003 in Kaohsiung Chang Gung Memorial Hospital in Taiwan, we observed 30 patients with scrub typhus, and 29 of them had liver function abnormality. In these patients, we found 89.3% with elevated aspartate aminotransferase (AST) levels, 91.7% with elevated alanine aminotransferase (ALT) levels, 84.2% with elevated alkaline phosphatase (ALP) levels, and 38.5% with elevated total bilirubin levels. In our study, there is a close relationship between scrub typhus and impaired liver function tests. Therefore, if patients are found with fever of unknown origin and abnormal liver function, we should take scrub typhus into consideration.     

Key differentiating features between scrub typhus and hemorrhagic fever with renal syndrome in northern China

Both scrub typhus and hemorrhagic fever with renal syndrome (HFRS) are severely epidemic in northern China and often present with acute undifferentiated fever. To correctly distinguish the two diseases at an early stage, we collected and compared clinical and routine laboratory data of 46 patients with confirmed scrub typhus and 49 patients with confirmed HFRS presenting to the outpatient departments of three town hospitals in northern China. Most patients with HFRS but none of the patients with scrub typhus had hemorrhagic manifestations. Retro-orbital pain, lumbar back pain, flank tenderness, proteinuria, and occult blood in urine often occurred in patients with HFRS. However, skin eschar, regional lymphadenopathy, and maculopapular rash were more commonly found in patients with scrub typhus. In addition, platelet counts in patients with HFRS were significantly lower than in patients with scrub typhus. These findings will be useful for physicians to distinguish scrub typhus from HFRS.     

Autopsy case of acute liver failure due to scrub typhus

Scrub typhus (Tsutsugamushi disease) is an acute febrile disease caused by infection with Orientia tsutsugamushi transmitted by mites. Although patients with scrub typhus commonly display mild liver injury, few die of acute liver failure. We describe herein an autopsy case of acute liver failure due to scrub typhus, which was complicated by disseminated intravascular coagulation and showed rapid progression of liver injury just before death. Histopathological findings revealed submassive hepatocellular necrosis, inflammatory cell infiltration in Glisson’s capsules, and sporadic fibrin thrombi in the hepatic sinusoids. Cause of death was primarily associated with acute liver failure related to disseminated intravascular coagulation.